In the United States, the overall incidence of melanoma is increasing at a rate faster than any other cancer, with recent estimates for lifetime risk of developing invasive melanoma at 1/49 (Jemal et al., C. A. Cancer J. Clin. 57:43-66, 2007). The development of melanoma begins with the malignant transformation of normal human epithelial melanocytes (NHEM) located within the basement membrane of the skin, but the genetic changes associated with the progression of NHEM to melanoma are not well characterized (Bittner et al., Nature. 406:536-540, 2000; DeRisi et al., Nat. Genet. 14:457-460, 1996; Golub et al., Science. 286:531-37, 1999; Hanahan et al., Cell. 100-57-70, 2000; Seykora et al., Am. J. Dermatopathol. 25:6-11, 2003; Su et al., Nature. 406:536-540, 2000; Trent et al., Science. 247:568-571, 1990; Weyers et al., Cancer. 86:288-299, 1999). Similarly, the molecular mechanisms underlying further progression from a primary tumor to a metastatic melanoma are also inadequately defined.
There is a correlation between the thickness of the primary melanoma and its capacity to metastasize to the draining lymph node basin(s) and hematogenously (Haddad et al., Ann. Surg. Oncol. 6:144-149, 1999; Cascinelli et al., Ann. Surg. Oncol. 7:469-474, 2000). Once melanoma has metastasized by either route, the overall survival for patients greatly diminishes (Balch et al., Cancer. 88:3635-3648; 2001; Balch et al., J. Clin. Oncol. 19:3622-3634, 2001). Whereas patients with thin primary tumors are cured by surgery, patients diagnosed with metastatic melanoma (AJCC stage IV) have an overall poor prognosis, with 6 out of every 7 skin cancer deaths due to metastatic melanoma (Balch et al., Cancer. 88:1484-1491, 2000; Eton et al., J. Clin. Oncol. 16:1103-1111, 1998; Jemal et al., C. A. Cancer J. Clin. 57:43-66, 2007).